Oncotarget

Research Papers:

Genetic alteration profiling of patients with resected squamous cell lung carcinomas

Dan Tao, Xiaohong Han, Ningning Zhang, Dongmei Lin, Di Wu, Xinxin Zhu, Wenya Song and Yuankai Shi _

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Oncotarget. 2016; 7:36590-36601. https://doi.org/10.18632/oncotarget.9096

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Abstract

Dan Tao1,*, Xiaohong Han1,*, Ningning Zhang1, Dongmei Lin2, Di Wu1, Xinxin Zhu2, Wenya Song1, Yuankai Shi1

1Department of Medical Oncology, National Cancer Center/Cancer Hospital, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

2Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Yuankai Shi, e-mail: [email protected]

Keywords: squamous cell lung carcinoma, genetic alteration, next-generation sequencing, fluorescence in situ hybridization, targeted therapy

Received: February 20, 2016    Accepted: April 17, 2016    Published: April 29, 2016

ABSTRACT

In this study, we analyzed the genetic profiles of squamous cell lung carcinoma (SqCLC) to identify potential therapeutic targets. Approximately 2,800 COSMIC mutations from 50 genes were determined by next-generation sequencing. Amplification/deletion of SOX2, CDKN2A, PTEN, FGFR1, EGFR, CCND1, HER2 and PDGFRA were detected by FISH and expression of VEGFR2, PD-L1 and PTEN were examined by IHC. One hundred and fifty-seven samples of SqCLC were collected. Somatic mutations was identified in 73.9% of cases, with TP53 (56.1%), CDKN2A (8.9%), PIK3CA (8.9%), KRAS (4.5%) and EGFR (3.2%). Gene copy number alterations were identified in 75.8% of cases, including SOX2 amplification (31.2%), CDKN2A deletion (21.7%), PTEN deletion (16.6%), FGFR1 amplification (15.9%), EGFR amplification (14.0%), CCND1 amplification (14.0%), HER2 amplification (9.6%) and PDGFRA amplification (7.6%). Positive expression of VEGFR2 and PD-L1 and loss of PTEN expression were observed in 80.5%, 47.2%, and 42.7% of cases, respectively. Multivariate analysis showed that positive expression of PD-L1 was an independent favorable prognostic factor for DFS (HR = 0.610; P = 0.044). In conclusion, nearly all (93.6%) SqCLC cases harbored at least one potential druggable target. The findings of this study could facilitate the identification of therapeutic target candidates for precision medicine of SqCLC.


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